Benzodiazepines intake may increase miscarriage risk

POLAND: Benzodiazepines are the drugs used for the treatment of anxiety during pregnancy. A new study has however found that women taking benzodiazepines for anxiety treatment are at significantly increased risk for spontaneous abortion.

These are the results of a large-scale study presented at the European Psychiatric Association (EPA) 2019 Congress.

The study was conducted by Anick Bérard, from the Faculty of Pharmacy, University of Montreal, Quebec, Canada, and colleagues, who evaluated more than 27,000 cases of spontaneous abortion and 1.3 million unaffected pregnancies during at 17-year period from an ongoing study.

The investigators gathered data from the ongoing Quebec Pregnancy Cohort, which covers 422,066 pregnancies between January 1998 and December 2015. They excluded women who had previously taken benzodiazepines and those who underwent induced or planned abortions. They included 27,149 women who experienced clinically detected, spontaneous abortion between the 6th and 19th week of pregnancy (mean, 13 weeks' gestation) during the study period.

Each case patient was then matched with up to five randomly selected women who had not experienced spontaneous abortion, yielding a control group of 134,305 women.

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Key findings of the study include:

• Incident use of benzodiazepines during pregnancy was associated with an 85% increase in the risk of having a clinically detected spontaneous abortion between the 6th and 19th week of pregnancy.


• Although the duration of action of the drug did not seem to affect risk, there was an increase in risk with increasing equivalent dose, so that women taking the highest doses had a more than 2.5-fold increased risk for spontaneous abortion.


• Women who experienced spontaneous abortion were significantly more likely to have used benzodiazepines for the first time during pregnancy than other women, at 1.4% vs 0.6% (odds ratio adjusted for comedication use and indication, 1.85).


• Women who experienced spontaneous abortion were also more likely than control women to be aged 35 years or older at gestation and to have been diagnosed with mood and anxiety disorders or insomnia in the 12 months prior to pregnancy.


• On analyzing benzodiazepine exposure more closely, they found that, with respect to the risk for spontaneous abortion, associations were similar for short-acting benzodiazepines and for long-acting drugs (adjusted odds ratios, 1.81 and 1.73, respectively). Short-acting drugs were defined as those having a duration of action of up to 24 hours.


• There appeared to be a dose-response effect with respect to a mean daily diazepam equivalent dose of benzodiazepines across the cohort.


• Certain benzodiazepines, such as diazepam (multiple brands), temazepam (multiple brands), bromazepam (multiple brands), alprazolam (multiple brands), and clonazepam (Klonapine, Roche), appeared to be more strongly associated with spontaneous abortions than other benzodiazepines.

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According to Bérard, benzodiazepine use seems to be associated with an increase in spontaneous abortion, regardless of type, regardless of the duration of action, and there seems to be a dose-response effect." "This equates to an increase in the absolute rate of spontaneous abortion from around 6% in the background population to around 10%," she explains.